Study to Improve Survival Among HIV-Exposed Infants in Botswana

Condition(s) targeted: HIV Infections; Neutropenia; Anemia

Intervention: cotrimoxazole prophylaxis (Drug); cotrimoxazole placebo (Drug); exclusive breastfeeding until 6 months of age (Behavioral); breastfeeding for 12 months (Behavioral)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Harvard School of Public Health

Official(s) and/or principal investigator(s):
Shahin Lockman, MD, MS, Principal Investigator, Affiliation: Harvard School of Public Health
Roger L Shapiro, MD, MPH, Principal Investigator, Affiliation: Harvard School of Public Health

The purpose of this study is to find ways to improve infant health and survival among infants whose mothers are HIV-infected but who do not themselves have HIV.

Official title: A Randomized Study of Cotrimoxazole Prophylaxis and Longer Breastfeeding Duration to Improve Survival Among HIV-Exposed Infants in Botswana

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: Survival

Secondary outcome:

HIV-free Survival

Safety of CTX prophylaxis

Morbidity and mortality

Detailed description: As improved MTCT prevention interventions reduce the number of HIV-infected infants in the antepartum and peripartum periods, interventions to improve HIV-free survival among HIV-uninfected infants are needed. Morbidity and mortality are increased among HIV-uninfected infants born to HIV-infected mothers, and reduced infant survival among HIV-exposed infants may lead to as many deaths as HIV infection itself. In Botswana, the use of formula feeding or shorter breastfeeding may worsen the problem of early infant mortality among HIV-exposed infants. The study will enroll pregnant or postpartum HIV-1-infected women, and their HIV-uninfected infants in Botswana. At 2-4 weeks of age, live HIV-uninfected infants will be randomized to receive either double-blinded cotrimoxazole (CTX) or placebo from 2-4 weeks through 15 months. In addition, breastfeeding (BF) infants will be randomized to BF until either 6 or 12 months of age. Children will be followed prospectively until 18 months of age. The primary endpoint will be survival at 18 months comparing all infants in the CTX vs. placebo arms, and by randomized duration of BF among those BF at randomization. Secondary endpoints will evaluate survival and morbidity/mortality at 12 and 15 months; HIV-free survival to 18 months; and the safety of CTX prophylaxis. Secondary observational objectives include comparing MTCT and mortality by initial feeding method (formula feeding or any BF > 1 month), and an analysis of maternal characteristics as predictors for initial feeding choice and HIV-free survival. All women and infants will receive standard antenatal and peripartum prophylaxis from the Botswana government for MTCT prevention (PMTCT), and will choose a feeding method with counseling. Breastfeeding infants will receive infant nevirapine (NVP) prophylaxis or will be protected from MTCT by the use of maternal HAART.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- HIV-infected women, > 26 weeks gestation and < 34 days postpartum.

- Women must be ¬> 18 years of age and willing/able to sign informed consent.

- Women and infants must be able to follow up regularly at a study clinic through 18

months postpartum.

- For Feeding Randomization Only: Women must be willing to breastfeed for up to 12

months, and to stop at 6 months, depending upon their feeding assignment. Exclusion Criteria:

- Antepartum women: Known infant anomalies resulting in a high probability that the

infant will not survive to 18 months.

- Postpartum women: Known HIV-infected infant, or infant medical condition making

survival to 18 months unlikely.

Princess Marina Hospital, Gaborone, Botswana

Athlone Hospital, Lobatse, Botswana

Scottish Livingstone Hospital, Molepolole, Botswana

Starting date: May 2011
Last updated: June 5, 2015